The goal of the Transgenic/knock-out Mouse Core (TMC) is to produce genetically modified mice as in vivo models for exploring the normal function of genes, and the role of genetic mutations in the etiology and treatment of cancer. The range of modifications that can be introduced into the genome of the laboratory mouse include integration of exogenous DMA (transgenes) useful in gain-of-function and cell labeling, and the precise excision (knock-out) or alteration (knock-in) of gene function that can be controlled both tissuespecifically and temporally. Transgenic and knock-in/knock-out mice are often the logical extension of studies initiated in vitro, and provide a model system with greater anatomical and physiological relevance to human disease. Genetically modified mice have been essential tools in elucidating the molecular underpinnings of many types of cancer, and supplement the traditional sub-cutaneous xenograft model for testing new anti-cancer therapies. During the most recent 12-month reporting period (January 2005 to December 2005) nine Cancer Center members from 3 programs and one non-aligned member used the transgenic/knock-out mouse shared resource. The number of users with peer-reviewed funding represented 66% of users overall. Annual budget for the core is $269,657, with 68% from the institution, 13% from user fees, and 19% ($50,000) requested from the CCSG.